Studies are being carried out to assess the potential influence of major histocompatibility complex (MHC) genes/gene products (HLA antigens) on disease process and outcome by determining the relative frequency of specific alleles in affected and control populations. The cohorts under study are HIV-infected homosexual men and hemophiliacs with appropriate HIV-1 seronegative control populations and HTLV-I infected individuals with and without virus-associated diseases. The HLA phenotype of individuals in these cohorts was determined by two methods: (1) serology, which identifies the products of the genes at the various loci on the surface of lymphocytes and (2) molecular techniques that identify different alleles at a particular locus at the DNA level. We have assembled the primers and probes and developed specific techniques that utilize the polymerase chain reaction to detect the following numbers of alleles at each of the following HLA loci: 39-DRB1, 3-DRB3, 4-DRB4, 2- DRB5, 8-DQA, 12-DQB, 2-DPA, 24-DPB, 4-TAP1, and 4-TAP2. The new techniques developed, as detailed in last year's reports, are now employed in HLA typing. Of particular importance has been the use of DNA prepared from serum from individuals who have died of AIDS. Mapping within the MHC are genes designated TAP1 and TAP2 that encode products that are critical for class I antigen presentation. We have determined the 4 alleles of each of these genes in a panel of reference HLA-typing B-cell lines and in CEPH families and define their location in the gene map relative to other MHC (HLA) genes. These studies allowed localization of the recombination regions relating to flanking genes as well as expanding the number of haplotypes that can be recognized in the general population. In analysis of HLA allele and haplotype frequencies in a cohort of 127 HIV-1-infected gay men, we found certain HLA haplotypes to be more frequent in the 70 individuals developing AIDS in a 10-year follow-up compared to those who have not developed the disease. This data establishes the importance of host MHC in regulating the response to HIV-1 infection and thus to the development of AIDS.